Molecularly imprinted polymer-electrochemical sensors are a promising approach for detecting non-electrochemically active contaminants such as per- and polyfluoroalkyl substances. However, exposure of poly(ortho-phenylenediamine) based molecularly imprinted polymer films to strongly acidic conditions can alter the polymer environment and complicate interpretation of electron mediator-based electrochemical readout. In this study, we examined how low pH exposure influences the response of a perfluorooctanoate templated poly(ortho-phenylenediamine) molecularly imprinted polymer - electrochemical sensors by comparing four commonly used electron mediators with different charge states: ferrocenemethanol, ferrocyanide, ferricyanide, and ruthenium (III) hexamine. Apparent binding affinity constants (KA) derived from Langmuir isotherm models, together with ratiometric comparisons of normalized current decreases, showed that mediator dependent trends changed after acidic pH exposure of the polymer. Charged mediators exhibited larger perturbations in apparent sensor response, whereas the neutral mediator, ferrocenemethanol, showed the most consistent performance across the conditions examined. These results are consistent with the interpretation that changes in the protonation state of the poly(ortho-phenylenediamine) film influence mediator access and interactions within the sensing environment, thereby biasing the mediator based current response. Overall, this work highlights that mediator choice can strongly affect the apparent performance of poly(ortho-phenylenediamine) based molecularly imprinted polymer - electrochemical sensor after exposure to low pH and should be considered carefully when interpreting sensor response under challenging conditions.
